HAMLET forms annular oligomers when deposited with phospholipid monolayers

Journal of Molecular Biology
Anne BaumannØyvind Halskau

Abstract

Recently, the anticancer activity of human α-lactalbumin made lethal to tumor cells (HAMLET) has been linked to its increased membrane affinity in vitro, at neutral pH, and ability to cause leakage relative to the inactive native bovine α-lactalbumin (BLA) protein. In this study, atomic force microscopy resolved membrane distortions and annular oligomers (AOs) produced by HAMLET when deposited at neutral pH on mica together with a negatively charged lipid monolayer. BLA, BAMLET (HAMLET's bovine counterpart) and membrane-binding Peptide C, corresponding to BLA residues 75-100, also form AO-like structures under these conditions but at higher subphase concentrations than HAMLET. The N-terminal Peptide A, which binds to membranes at acidic but not at neutral pH, did not form AOs. This suggests a correlation between the capacity of the proteins/peptides to integrate into the membrane at neutral pH-as observed by liposome content leakage and circular dichroism experiments-and the formation of AOs, albeit at higher concentrations. Formation of AOs, which might be important to HAMLET's tumor toxic action, appears related to the increased tendency of the protein to populate intermediately folded states compared to the native protein, t...Continue Reading

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Citations

Nov 8, 2012·Future Oncology·James Ho C SCatharina Svanborg
Feb 28, 2013·The FEBS Journal·Christel R BrinkmannDaniel E Otzen
Jan 11, 2017·Biochimica Et Biophysica Acta. Biomembranes·Øyvind StrømlandØyvind Halskau
Aug 23, 2020·Biomolecules·Eugene A Permyakov
Jul 3, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Olena DobrovolskaØyvind Halskau

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